Trauma is a major health care problem in the United States. With improved emergency medical care more injured patients are surviving the initial injury only to sustain major complications and undergo prolonged hospitalization before recovery. Others often die after weeks of intensive care. The cause(s) of the posttraumatic responses remains unknown, but is somehow related to the hypercatabolic response to injury, tissue breakdown, immunosuppression, chronic inflammation and/or infection. The objectives of this proposal are, first, to determine the mediators of the metabolic responses following injury. The role of interleukin-1, prostaglandins, endotoxin, and other inflammatory mediators will be determined in both humans and experimental animals. The effect of these mediators on macrophages in the wound, circulating monocytes and neutrophils, and on other tissues such as lung, skeletal muscle, and liver will be assessed. The mechanisms that lead to net catabolism of skeletal muscle proteins in injured patients will be determined, and the function of muscle-derived amino acids in other tissues assessed. The effect of growth hormone on net protein catabolism will be investigated, especially when administered with hypocaloric feedings. The safety and efficacy of adding the amino acid glutamine to intravenous nutritional formulas will be determined. The significance of the anticipatory response to feeding will be assessed, and the role of neural regulation in this system determined.